Substances important as physiologically active substances have been found in various metabolites produced by actinomycetes. In particular, many compounds structurally having polyketide as a core structure (hereinafter referred to as polyketide compounds) have been found. For example, the following various compounds having a biological activity have been known: erythromycin, josamycin, tylosin, midecamycin and mycinamicin known as antibacterial substances; nystatin and amphotericin known as antifungal substances; milbemycin and avermectin known as insecticidal substances; tacrolimus and rapamycin known as immunosuppressive substances; and daunomycin, adriamycin, and aclacinomycin known as antitumor substances.
As one type of such compounds, there are a group of polyketide compounds having an excellent antitumor activity, named as herboxidiene. Herboxidiene is a compound represented by the formula (I) as shown below, which has been first discovered from a culture product of an actinomycete strain, Streptomyces chromofuscus A7847 (see Non Patent Literature 1). Thereafter, 5 or more types of analogues, including herboxidiene as a typical example, have been discovered from several actinomycete strains (see patent Literatures 1 and 2).

On the other hand, many facts have been known about the biosynthetic mechanism of such polyketide compounds. It has been said that the aforementioned variety of polyketide compounds share the same biosynthetic mechanism, and that the mechanism is extremely similar to the biosynthesis of fatty acid. That is to say, polyketide compounds are biosynthesized by steps of continuously condensing lower fatty acid such as acetic acid or propionic acid, and then subjecting the carbonyl group at position β of the extended acyl group to ketone reduction, dehydration, or enoyl reduction, according to the same method as fatty acid synthesis. It has been said that various repetitive steps of synthesizing these many polyketide compounds are regulated by the multifunctional enzyme complexes of polymers having different active sites (domains) necessary for individual reaction catalytic activities. A general reaction mode of polyketide biosynthesis is summarized, for example, in Non Patent Literatures 2 and 3.
It has been revealed that a DNA sequence encoding polyketide synthase generally encodes all activities necessary for the synthesis of polyketide skeletons, and that the DNA sequence is constituted with repeating units comprising a condensation step and a modification step after the condensation, namely, with modules. Each module participates in a specificity of a specific carboxylic acid constitutional unit contained in each condensation step and in a modification function after specific condensation. For example, Non Patent Literature 4 describes a gene encoding polyketide synthase involved in the biosynthesis of pikromycin by Streptomyces venezuelae ATCC15439. Patent Literature 3 describes the structure of a gene encoding erythromycin polyketide synthase of Saccharopolyspora erythraea. This gene is constituted with 6 modules, and each module conducts a single condensation step. That is, the precise sequence of acyl side chain elongation and the modification of the elongating chain are determined by gene information existing in each module.
Moreover, after the synthesis of polyketide skeletons by polyketide synthase, such variety of polyketide compounds are often modified by an enzyme catalyzing modification reactions such as hydroxylation, epoxidation or methylation (hereinafter referred to as a modifying enzyme, at times), so that they are converted to final metabolites. It has been revealed that a group of genes involved in these productions; namely, enzymes necessary for the biosynthesis of such final metabolites, and genes encoding regulatory factors necessary for the regulation of the productions (hereinafter, this gene group involved in biosynthesis may be generically referred to as solely “a biosynthetic gene”, at times), are generally disposed in the genome of producing bacteria or in a DNA region on a plasmid, while forming a cluster.
If the information of the nucleotide sequence of a gene encoding polyketide synthase is determined, it becomes possible to modify a domain based on the obtained information, so as to change the size of a carbon chain and the functional group of the carbon at position β during a condensation process. For example, Non Patent Literature 5 describes that a novel derivative of erythromycin can be produced by selectively inactivating a specific domain in the polyketide synthase gene of erythromycin. Moreover, by replacing the domain of each module with another one, it becomes possible to produce a predictable, novel compound. For example, Non Patent Literature 6 describes that a variety of novel compounds can be produced by replacing several domains in the polyketide synthase gene of erythromycin with other domains.
Furthermore, if the nucleotide sequence of a biosynthetic gene cluster comprising a gene encoding a modifying enzyme (hereinafter referred to as a modifying enzyme gene, at times) is determined, it becomes possible to selectively modify the modifying enzyme gene based on the obtained information, so as to produce a predictable, novel compound. For example, Non Patent Literature 7 describes that a novel derivative, 6-deoxyerythronolide B, can be produced by deleting a hydroxylase gene eryF, existing in the neighborhood of the polyketide synthase gene of erythromycin.
Further, there is a case in which unnecessary by-products can be reduced and a single ingredient of interest can be produced by activating the expression of a modifying enzyme gene. In order to activate gene expression, there have been generally known methods, such as the activation of transcription by the substitution of a promoter, an increase in the number of gene copies using a multicopy vector, and the improvement of an enzyme activity by the introduction of a mutation into a gene. Moreover, there is a case in which productivity can be enhanced by activating or inactivating a regulatory gene by the same above methods.
Furthermore, there is also a case in which, using a different strain, a polyketide compound of interest can be produced by obtaining a gene encoding such biosynthetic gene cluster, and then by introducing the obtained gene into the different strain according to an adequate method. As a different strain used herein, microorganisms, and particularly, Escherichia coli that can be cultured in a short time, can be advantageously used. For example, Non Patent Literature 8 describes that a 6-deoxyerythronolide B of interest as an erythromycin precursor can be efficiently produced by incorporating a polyketide synthase gene into Escherichia coli. 
Still further, Patent Literature 4 describes: a polypeptide involved in the biosynthesis of a macrolide compound, pladienolide, that is one type of polyketide compound; a DNA encoding the polypeptide and a variant thereof; a transformant retaining a part or the entire of the DNA or the variant thereof; and a method for producing the macrolide compound, pladienolide, using the transformant.